Submissions for variant NM_000251.2(MSH2):c.2714C>G (p.Thr905Arg) (rs267608022)

Minimum review status:		Collection method:
Minimum conflict level:
		ClinVar version:

Total submissions: 4

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000203618	SCV000107568	likely benign	Lynch syndrome I	2015-11-24	reviewed by expert panel	research
Invitae	RCV000076539	SCV000166276	uncertain significance	Hereditary nonpolyposis colon cancer	2018-10-01	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with arginine at codon 905 of the MSH2 protein (p.Thr905Arg). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs267608022, ExAC 0.003%). This variant has been reported in a family affected with colorectal cancer (PMID: 8880570). ClinVar contains an entry for this variant (Variation ID: 91037). Experimental studies have shown that this missense change does not significantly impact MSH2 activity (PMID: 9774676, 12124176). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000129528	SCV000184304	uncertain significance	Hereditary cancer-predisposing syndrome	2018-02-21	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence
GeneDx	RCV000424772	SCV000518413	likely benign	not specified	2017-08-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.